R01CA263770

Systemic Racism and Biological Embodiment of Risk in Breast Cancer Mortality - Black women experience much higher breast cancer mortality than any other race/ethnic group in the US. Despite extensive investigation, the known causes to date do not adequately explain this mortality gap.

Largely missing in the disparities literature is a rigorous examination of systemic racism – i.e., how exposure to an overarching environment of systemic racism (SR) might impact breast cancer outcomes in Black women. Multiple lines of evidence, when considered together, indicate this exposure merits investigation.

SR (e.g., perceived discrimination, residential segregation) is associated with a range of adverse health effects in Blacks, and chronic psychosocial stress due to SR can become embodied via hyperactivation of the hypothalamic pituitary adrenal (HPA) axis, leading to inflammatory, metabolic, and epigenetic dysregulation.

Thus, we hypothesize that exposure to SR leads to alterations in key biological pathways, which in turn contribute to excess breast cancer mortality in Black women. No empirical study has directly tested this hypothesis in a single cohort.

To address this gap, we will generate a new prospective cohort with 2,498 incident breast cancer and 2,678 sub-cohort random sample from two parent cohorts – the Reasons for Geographic and Racial Differences in Stroke (REGARDS) and Southern Community Cohort Study (SCCS) cohorts.

Both parent cohorts oversampled Blacks and include participants from Southern states with a history of SR and obtained extensive baseline and biomarker data, enabling us to measure biomarkers of inflammation and metabolic dysregulation.

We will newly assess measures of SR at the structural and interpersonal levels and characterize epigenome-wide DNA methylation profiles. Our study will conduct the first thorough prospective evaluation of the distinct influence of SR, above and beyond other racially patterned risk factors, on breast cancer disparities in a large, diverse cohort.

By quantifying the distinct impact of SR on breast cancer mortality, and identifying pathways and biomarkers that mediate this association, our study will help improve the poor accuracy of breast cancer prognostic models in Black women, and inform primary prevention strategies focused on mitigating SR to reduce racial disparities in breast cancer mortality.

Duke University

TO IDENTIFY CANCER RISKS AND RISK REDUCTION STRATEGIES, TO IDENTIFY FACTORS THAT CAUSE CANCER IN HUMANS, AND TO DISCOVER AND DEVELOP MECHANISMS FOR CANCER PREVENTION AND PREVENTIVE INTERVENTIONS IN HUMANS. RESEARCH PROGRAMS INCLUDE: (1) CHEMICAL, PHYSICAL AND MOLECULAR CARCINOGENESIS, (2) SCREENING, EARLY DETECTION AND RISK ASSESSMENT, INCLUDING BIOMARKER DISCOVERY, DEVELOPMENT AND VALIDATION, (3) EPIDEMIOLOGY, (4) NUTRITION AND BIOACTIVE FOOD COMPONENTS, (5) IMMUNOLOGY AND VACCINES, (6) FIELD STUDIES AND STATISTICS, (7) CANCER CHEMOPREVENTION AND INTERCEPTION, (8) PRE-CLINICAL AND CLINICAL AGENT DEVELOPMENT, (9) ORGAN SITE STUDIES AND CLINICAL TRIALS, (10) HEALTH-RELATED QUALITY OF LIFE AND PATIENT-CENTERED OUTCOMES, AND (11) SUPPORTIVE CARE AND MANAGEMENT OF SYMPTOMS AND TOXICITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO STIMULATE TECHNICAL INNOVATION, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, AND FOSTER PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS.

93.393 - Cancer Cause and Prevention Research

National Cancer Institute (NCI) [HHS - NIH]

Durham, North Carolina 277012124 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 383% from $824,471 to $3,981,466.